Oral transmission of HIV is one of the factors fueling the current AIDS pandemic. Here we utilize the simian immunodeficiency virus (SIV)/macaque AIDS animal model to investigate the early events following oral transmission. We hypothesize that the very early events in mucosal transmission are crucial to determining whether or not an infection occurs. By investigating these earliest events, a clear picture will emerge as to how infection via the oral route occurs and why a successful HIV/SIV infection is only observed after some oral inoculations. A fluorescently labeled SIV (SIVmac239gfp) will be used to enable us to identify the cell infected very early after the virus inoculation (Aim 2). Low doses of virus will be used to assess the role of an inflamed gingivitis mucosa in SIV transmission (Aim 2). The role of gingivitis will be assessed in juvenile macaques and the role of inflamed gums associated with the cutting of teeth will be assessed in infants. Transient infections represent an important disease outcome in which the virus is detected several weeks post-inoculation but can not be detected at later time points. We will investigate both virologic and immunologic aspects of transient infections (Aim 3). This study will include an assessment of the number of SIV responsive T-cells in macaques utilizing a new assay developed by Dr. Louis Picket at the University of Texas Southwestern Medical Center. PBMC's will be obtained from SIV vaccinated, SIV infected and uninfected macaques and assessed for the ability to produce cytokines in the presence of SIV antigens through a flow cytometric analysis. In total these studies are designed to assess the entry of virus via the oral mucosa, follow the virus as it disseminates throughout the macaque and to assess the factors which influence a successful or abortive oral transmission.